Dr. mike Overton presented this information for DAIReXENT on Monday, March 18, 2013. For more information, please see our archived webinars page at www.extension.org/pages/15830/archived-dairy-cattle-webinars.
The tremendous physical and physiological changes that the cow undergoes from late gestation into early lactation require energy and immune function. To appreciate the need to manage EB and IF, one just needs to consider the tremendous changes that the dairy cow goes through during the V90. During the Far-Off dry and Close-up periods when the cow is not lactating, her body weight increases slightly due to fetal growth, but her body condition should be stable. During these periods the dry matter intake is stable and lower than during lactation since the cow is not producing milk. After calving, we see a rapid increase in milk production and a response from the cow to increase intake and mobilize body reserves to meet the needs initiated by lactation.
We will look at these 2 main categories of the immune system (innate immunity and acquired immunity) individually, but remember, the immune system is the total interactions between all the components.
This figure illustrates the layers of protection of the immune system. Generally, physical barriers (the first layer) are considered to be a part of the innate immune system.
Polymorphonuclear granulocytes are abbreviated PMNs. The most common PMN found in blood is the neutrophil so it is common to use the term PMN and neutrophil interchangeably. Neutrophils are considered the key phagocytic cell of the innate immune system. This is one of the reasons we will be talking a lot about neutrophils.
Source: Goff J. Transition Cow Immune Function and Interaction with Metabolic Diseases. Tri-State Dairy Nutrition Conference. April 22-23, 2008.
Far Off To Fresh Cow- Opportunities to Improve Transition Performance
Transition Period • Traditionally considered from -21 to 21-DIM • More apparent that transition actually starts at dry-off: – 90-day period that is critical for success – Far Dry, Close-up and Fresh Periods • Period of significant stress on all cows • Sets the stage for future productivity and repro performance 90-Day “Transition” Far Dry Period Close-up Dry Period Calving Fresh/ Early Lactation-60 -21 0 30 USDBUNON00529
Primary Take Away: Managing Energy Balance & Immune Function HelpsMitigate Impact of Transition Challenges• Cows undergo tremendous changes from late gestation to early lactation USDBUNON00529
Complex Interrelationships of Transition Cow Diseases Dotted line denotes tentative association USDBUNON00529
Transition Management Keys for Improved Health, Production and Reproduction1. Minimize feed intake depression and negative nutrient balance before calving (metabolic disease)2. Minimize risk and impact of dystocia3. Minimize risk and impact of hypocalcemia (milk fever)4. Minimize risk and impact of infectious disease (mastitis, metritis, etc)5. Promote rapid return to positive nutrient balance (maximize rise in feed intake after calving) Dry-off Calving Far-Dry Close-up/ Fresh Springer USDBUNON00529
Transitional Management Key # 1: Minimize Negative Nutrient Balance and Drop in Feed Intake Before Calving• The level (and amount of change) of the feed intake before calving has a huge impact on: – Immune function – Risk of metabolic disease (ketosis) – Start-up milk – Feed intake after calving• It is common to hear… “We need to maximize feed intake in close-up cows”! (?)• However, a more correct approach would be to minimize the decrease in voluntary feed intake USDBUNON00529
NEFA’s, Fat and Ketosis…• Triglyceride: – 3 Non-esterifed fatty acids – Glycerol backbone• Fat mobilization increases: – Due to increased energy demand (lactation) – As a consequence of increased GH – As a consequence of stress response (epinephrine) – Excessive mobilization can lead to ketosis• Fat mobilization blocked by “normal” insulin USDBUNON00529
What is Ketosis?• Defined as increased ketone bodies in the blood – Acetoacetate – Beta-hydroxybutyrate (BHB) – Acetone• Excreted in the milk and urine• Characterized by hypoglycemia, ↑ NEFA and ↑ circulating ketone bodies, depressed appetite USDBUNON00529
Ruminant Physiology• Ruminants do not obtain glucose directly from the diet• Fermented carbohydrates converted to VFA’s by rumen – Acetate – used in fatty acid synthesis • Source – fiber (hay, silage, some by-products) – Propionate – major substrate for gluconeogenesis • Source – fermentable carbohydrates such as starch & sugar – Butyrate – converted to ketones for energy • Source – produced in rumen but also ingestion of preformed• Constant state of gluconeogenesis (making glucose) USDBUNON00529
Fetal Metabolism – Late Pregnancy• Most energy needs of the fetus are supplied by glucose, lactate, and amino acids from the dam – Glucose uptake – passive – AA uptake via active placental transport (independent of maternal blood concentration) – During hypoglycemia, fetus compensates by using more AA for energy Uterine UptakeNutrient Maternal Supply (g/d) Grams/d % of Maternal SupplyGlucose 1,476 666 46Amino Acids 998 718 72Bell, A. W. 1995. J Animal Sci 73(9):2804-2819. USDBUNON00529
Rapid Acceleration in Nutrient Needs Around Calving • Within a few days of calving, mammary requirements increase as compared to uterine demands just before calving: – Glucose 2.7 X pregnant uterus – Amino acids 2.0 X pregnant uterus – Fatty acids 4.5 X pregnant uterus – Total “Energy” ~3 X pregnant uterus • Despite these needs, feed intake is low, resulting in… – Negative energy balance: -10 to -15 Mcal/d (or more) – Negative protein balance: - 500 to -600 g/d (or more)Bell, A. W. 1995. J Animal Sci 73(9):2804-2819. USDBUNON00529
How Does the Modern Dairy Cow Do It?• Two major ways: – Alters glucose metabolism Mediated in • Glucose sparing part by • Increased gluconeogenesis from amino acids somatotropin – Mobilizes body tissues (fat and protein) (growth • Leads to increased NEFA’s hormone)• Liver is crucial in these adaptations Day relative to calving -21 11 22 Liver weight (lbs) ~ 19 ~ 19 ~ 21 Oxygen uptake 35 76 80 (moles/d)Adapted from: Reynolds et al, 2003. J Dairy Sci 86(4):1201-1217. USDBUNON00529
Adaptations at Parturition and Onset of Lactation1,2 Adipose Tissue Rumen lipolysis size de novo fat synthesis absorptive capacity uptake of preformed fatty acids rate of nutrient absorption re-esterification of fatty acids Mammary gland # secretory cells nutrient useLiver supply of blood size rate of gluconeogenesis protein synthesis Muscle ketogenesis glucose utilization protein synthesis protein degradation1Bauman, D. E. and W. B. Currie. 1980. J Dairy Sci 63(9):1514-1529.2Ingvartsen, USDBUNON00529 K. L. and J. B. Andersen. 2000. J Dairy Sci 83(7):1573-1597.
What Can We Do in the Far Dry Group toBetter Manage Feed Intake and Improve Postpartum Performance? • Control the energy intake in far dry cows • Manage environment to minimize stress and weight loss during dry period • Provide adequate and comfortable resting access • Beware long days dry USDBUNON00529
Close-Up Cows: a Critical Group to Manage Properly • Can have large drops in feed intake • More sensitive to stressors • Must deal with decline in immune function • Must deal with calcium challenges • Typically, this is when negative energy balance starts – Making colostrum and supporting the fetus USDBUNON00529
Effect of Prepartum Stocking Density on Production• 2001 field trial to evaluate dry cow feed additive – 1st calf heifers grouped with older cows (pre- and post- fresh)• Two-row pens with lockups, pre and post-fresh• Pre-fresh stall stocking density ranged from 62 to 138% of stalls• No stall overstocking in post-fresh pens USDBUNON00529G.R. Oetzel, unpublished work, 2003
Pre-fresh Stocking Density and 90 Post-fresh Milk Yield 80 70Milk, lbs/day 60 132 1st lactation cows modeled 50 1.6 lb/d lost for each 10% increase in pre- 40 fresh stocking density P<.01 for effect of presd on milk yield 30 3 13 23 33 43 53 63 73 83 Days in Milk 80% presd 100% presd 120% presd USDBUNON00529 G.R. Oetzel, unpublished work, 2003
Prepartum Stocking Density (freestalls) 1st Test Milk (Lact 2+) 100 95 1st Test (Lbs Milk) 90 85 80 75 70 70% 80% 90% 100% 110% 120% 130% 140% 150% 160% 170% 180% 190% 200% Stocking Density (at Calving)Overton and Sischo, unpublished results, 2004 USDBUNON00529
Typical Ration Guidelines1 Far Dry High Forage Close-Up Crude Protein 12.5-13% 14 – 15.5% NEL 0.58-0.62 Mcal/lb 0.62-0.65 Mcal/lb MCal 14-15 MCal NEL 15-17 MCal NEL Metabolizable Protein 900 – 1000 g 1100 - 1200 g NFC 24 - 28% 28 - 32% Starch 12 - 16% 16 - 19% NDF 50% 42 - 45% Vit A 80,000 IU 100,000 IU Vit E 1000 – 1200 IU 2000-3000 IU DMI ~ 30 lbs 24 – 28 lbs1Nutrition recommendations adapted in part from Tom Overton, presentation at 2012 U. Minn. NCE- USDBUNON00529DVM, St. Peter, Minn)
Transitional Management Key # 2: Reduce Risk and Impact of Dystocia• Negative effects on: – Calves • More likely to die at birth • More likely to get sick before weaning • Higher death rate prior to weaning – Cow performance • Greater risk of premature culling, especially in first lactation • Reduced milk production • Greater risk of metritis • Reduced reproductive performance USDBUNON00529
Reducing the Effects of Dystocia• Feed and manage heifers to calve at 22-24 months with adequate frame size but not fat – Need to measure heights AND weights periodically to check program – Breed based on frame size, not age• Provide clean, dry stress-free area for calving• Provide proper calving assistance training to employees• Improve reproductive efficiency in milking cows to reduce # of fat cows in herd – Long days in milk (poor repro) and low milk increase risk of high BCS• Use calving ease sires and reduce/avoid use of natural service bulls in heifer pens USDBUNON00529
Milk Fever• Subclinical hypocalcemia affects many cows• Clinical hypocalcemia normally < 5-6%• Increased risk for – Older cows (3+ parity) – Jerseys – High producing cows• Associated with increased risk of – Ketosis, LDA, impaired reproductive performance Erb, H. N. and Y. T. Grohn. 1988. J Dairy Sci 71(9):2557-2571. USDBUNON00529
HYPOCALCEMIA (clinical or subclinical) Smooth muscle function Rumen, digestive tract motility Immune Uterine motility function RP Involution DA Feed intake Body reserve mobilization EB Metritis Ketosis MILK YIELD FERTILITY Hypocalcemia, feed intake, and immune function are interrelated – All are critical for early lactation production and health USDBUNON00529
Management of Milk Fever (clinical and subclinical hypocalcemia) Management of Dry Cow Nutrition• Traditional approach: • DCAD approach – Restrict Ca intake prepartum – Balance cations (Na and – < 40 g/d K) and anions (Cl and S) – Actually needs to be < 20 g/d – Goal: • Less than the 30 g/ day that is • Negative DCAD needed by the cow • Slight metabolic acidosis – Results in activation of PTH, – Result: increased tissue osteoclasts and renal tubular responsiveness to PTH absorption • System is ready for increased demand at calving USDBUNON00529
Transitional Management Key # 4: Minimize Impact of Infectious Disease• Two key infectious diseases that impact fresh cows: – Mastitis – Metritis• Means to lower risk of infection: – Good immune function PRE- and POST-Partum – Maintain adequate calcium balance – Minimize impact of environment – Minimize risk/ impact of dystocia – Minimize risk of metabolic diseases USDBUNON00529
ImmunitySpecific organs, tissues, cells, and molecules worktogether to form the immune system and help protect thecow from infectious disease.To help understand such a complex system, immunologistswill commonly group the functions of the immune systeminto two categories 1. Innate immunity, also known as native immunity 2. Acquired immunity, also known as adaptive immunity USDBUNON00529
The Big Picture • The defense against infective microbes works as a series of layers of increasing levels of protection. When invading microbes overtake the first layer, the next layer attempts to stop them. This defense is possible by – Early reactions of the innate immune system (minutes to hours) – Later events of the acquired immune system (hours to days) • Both systems work in a coordinated fashion and overlap to a certain degreeTizard IR. Veterinary Immunology - An Introduction. 8th ed. St. Louis, MO: Saunders Elsevier; 2009. USDBUNON00529
The Innate Immune Response Physical Barriers• The innate immune system represents the first line of active defense against invading pathogens Inflammatory Response• The non-specific or innate immune system consists of three major systems 1. Physical barriers 2. Inflammatory responses Phagocytic Response1 3. Phagocytic response1(http://classes.midlandstech.edu/carterp/Courses/bio225/chap16/lecture3.htm , last accessed on 2/7/13) USDBUNON00529
Cells of the Innate Immune System• Neutrophils • Monocytes/Macrophages • Neutrophils (a type of granulocyte) are • Monocytes are only found in the the first of the circulating defense cells blood. When they enter the tissue they are called to respond and migrate to sites of macrophages. Macrophages aid infection. Neutrophils bind to and in phagocytosis of foreign cells phagocytose invading microorganisms. They are considered the key phagocytic cell of the innate immune system USDBUNON00529
Acquired Immune Response• The acquired immune system has to recognize and destroy foreign invaders and then retain their memory so that if the animal encounters the same organism again, the immune system will respond more quickly and effectively• Developing acquired immune response is a complex interaction between the animal and pathogen and will be dependent upon the dose and strength of the pathogen as well as the duration of exposure USDBUNON00529
Characteristics of the Acquired Immune System• Slower response than the innate immune system• Requires the presence of specific antigens• Acquires the ability to produce specific antibodies to antigens• Memory response which is amplified by repeated exposure• Two major components of the Acquired Immune System 1. Humoral immunity (antibodies) 2. Cell mediated immunity• Acquired immunity is the basis behind all vaccination strategies USDBUNON00529
Lymphocytes• The key white blood cell of the acquired immune response is the lymphocyte• Lymphocytes are the cells that specifically recognize and respond to foreign antigens• Lymphocytes circulate between the blood stream and the lymphatic system, unlike other white blood cells that once they enter the tissue they stay there• There are two major subpopulations of lymphocytes that differ in how they recognize antigens and in their functions – B Lymphocyte – T Lymphocyte USDBUNON00529
Periparturient Immune Suppression• Endocrine changes and physiologic stress of the transition period lead to compromised (i.e. suppressed) immune function.1 While this compromise (i.e. suppression) is multifactorial, it is related to: – Energy balance – Ketones and non-esterified fatty acids (NEFA) – Calcium metabolism – Glucocorticoids• Adequate nutrition, a clean environment, and management decisions help manage immune function in the periparturient period. 1. Goff J 2008. Transition Cow Immune Function and Interaction with Metabolic Diseases USDBUNON00529
Immune Dysfunction as a Contributing Cause of Retained Placenta • Theory proposed by Gunnink1-3 – When blood supply to placenta ceases, it becomes a “foreign body” – Maternal immune system must recognize and attack – Cotyledons from RP cows had less leukocyte chemoattractant than cotyledons from normal cows – Reduced chemotaxis in neutrophils from RP cows • Follow-up work by Kimura et al4 – Neutrophils from RP cows had lower function pre-calving1Gunnink JW. Vet Q. Apr 1984;6(2):49-51.; 2 Gunnink JW. Vet Q. Apr 1984;6(2):52-54.; 3Gunnink JW. Vet Q. Apr 1984;6(2):55-57. USDBUNON005294Kimura et al, 2002. J Dairy Sci 85:544-550
Periparturient Energy Metabolism, Immune Function and DiseaseSevere or Poor Response to Hypocalcemia Negative Energy Balance (clinical or (i.e., low DMI) subclinical) Reduced Function of Neutrophils And/or Lymphocytes Increased Disease Susceptibility Mastitis Retained Uterine Infections • Incidence Placenta • Endometritis • Severity • Chronic infections? • Duration USDBUNON00529
Transitional Management Key # 5: Promote Rapid Return to Positive Energy Balance (Maximize Fresh Cow Feed Intake)• Goal: Reduce stressors holding – Rapid rise in feed intake cows back! A. Reduce the impact of fresh• Result: cow disease – Less risk of ketosis problems – Ketosis, metritis, MF – Higher first test B. Improve cow comfort – Higher peak milk C. Provide consistent high – Less weight loss quality feed – Reduced time to first ovulation D. Watch stocking density USDBUNON00529
Time Management (Cow’s Perspective)Milking time 2-3 hrs (3)Eating/ Drinking 5-6 hrs (5)Socialization/ walking 2-3 hrs (2)Standing in stalls 1-2 hrs (1)Lying 12-14 hrs (13) 24What about Management??? Fresh Cow Monitoring Breeding Milking TAI Eating etc. Socializing Standing LyingGrant, R. J. 2009. Pages 7-17 in Proc. Western Dairy Management Conference, Reno, NV. USDBUNON00529
Time Mis-Management (Cow’s Perspective)Milking time 2-3 hrs (5)Eating/Drinking 5-6 hrs (4)Socialization/Walking 2-3 hrs (2)Standing in stalls 1-2 hrs (1)Forced lockup < 1 hr (2)Lying 12-14 hrs (10) 24• Consider: – -2 or -8 lb milk loss Milking – Extra 0.25 to 0.75 Eating BCS loss over 100 days Socializing Standing LyingGrant, R. J. 2009. Pages 7-17 in Proc. Western Dairy Management Conference, Reno, NV. USDBUNON00529
Dry Matter Intake is the Driver Behind Early Cyclicity, NOT Milk Production DMI (lbs) at DMI (lbs) Body wt loss Milk (lbs/d) -7 days early lact (30 DIM) Early Ov 33 45 -90 108 Late Ov 26 40 -150 109Butler 2006, Penn State Dairy Cattle Nutrition Workshop, 51-60. USDBUNON00529
*Five Transition Management Keys*1. Minimize DMI depression prepartum – Must meet MP and ME needs to the cow, calf and colostrum – Goal is to minimize risk of metabolic disease2. Minimize risk and effects of dystocia3. Minimize risk and effects of hypocalcemia/ hypomagnesemia4. Minimize the impact of mastitis and metritis – Optimize immunocompetence5. Promote rapid return to positive energy balance (Maximize rise in feed intake after calving) USDBUNON00529
Thanks For Your Attention! Michael Overton, DVM, MPVM (706) 248-4664 firstname.lastname@example.org USDBUNON00529